This month, another intranasal vaccine has gone into clinical trial in Europe. It’s the 32nd mucosal vaccine to start clinical testing &ndash…
Exciting News from Europe, and Roadblocks in the US (NextGen Covid Vax Update 26)
There are 2 pieces of exciting news from Europe this month. As anticipated, the European Commission has authorized Kostaive, the self-amplifying mRNA vaccine developed by Arcturus. The full independent European assessment is out, and it answers the burning question the developers’ publications had not: The self-amplifying mRNA generates more mRNA soon after injection, but, like the original mRNA, it is transient.
The other good news? An ambitious plan was announced for an intranasal vaccine that aims to prevent infection. It is going into clinical trial in France. That’s the 33rd mucosal vaccine to enter clinical trial globally. The new French vaccine was developed with a lot of public funding, and a major (though as yet unnamed) pharmaceutical company has already licensed the vaccine, with hopes it will make it into use in the not-too-distant future.
In other good news, there’s government funding in Japan to explore inhaled mRNA vaccine for respiratory diseases, as well as preclinical results for an intranasal mRNA vaccine in Singapore. There is also another vaccine aiming to be “variant-proof” going into a clinical trial in the US.
There’s news of turmoil and roadblocks for vaccines this month, though, from the US. I begin this post there. After that, I have the news from the last month broken down into 3 categories of next-generation Covid vaccines as usual (definitions below). Each section ends with an overview of vaccines in the category – and each has a link to skip over that straight to the next news section. There is news on trials and preclinical results for vaccines in the first 2 categories – but no news or results to report in the third category (pancoronavirus vaccine).
ICYMI:
- An introduction to self-amplifying mRNA, plus my compendium on getting ready for more mRNA fear-mongering.
- Check out my May 2024 post, “When will we get a sterilizing Covid vaccine?”
- Roadblocks in the US
- Mucosal vaccine news
- Durable or “variant-proof” vaccine news
- Pancoronavirus vaccine news
- Addendum 1: List of authorized vaccines (with countries)
- Addendum 2: Table of mucosal vaccines in clinical trials
- Addendum 3: Table of pancoronavirus vaccines with preclinical results
- Addendum 4: Definitions of vaccine types
Roadblocks in the US
The impact of the new US regime is starting to hit vaccines, and threats of tariffs on imported drugs are contributing to the turmoil and uncertainties for pharmaceutical manufacturers. Let’s start with the recent setbacks for vaccines:
- The most advanced Project NextGen-funded trial has been put on a 90-day hold. Last month I reported that the oral vaccine from Vaxart had been given the go-ahead to fully recruit its 10,000-participant phase 2b “mini-efficacy” trial after an evaluation of safety in 400 people. Recruitment for the remaining 9,600 people was about to start. A government spokesperson claimed that “failed oversight have made it necessary to review agreements for vaccine production,” and they would judge whether they believe the Vaxart vaccine is a “safe, effective, and fiscal-minded vaccine technology.” The company can continue to monitor the group already vaccinated, but the company cannot bill for the next $230 million for the large trial.
- In January, the government had awarded Moderna a major contract to develop an mRNA vaccine against H5N1 avian influenza. That is now reportedly threatened by a review of “spending on messenger RNA-based vaccines.”
- The FDA meeting to determine the strains for the next round of seasonal influenza vaccine was cancelled, with no information about re-scheduling.
Meanwhile, one of the Project NextGen-funded companies, Geovax, issued a press release congratulating the new Health Secretary on his appointment, and claiming it “provides a significant opportunity for healthcare innovation, transparency, and public trust, reinforcing national priorities such as vaccine safety, diversified vaccine platforms, and strengthened domestic manufacturing” – which aligns, they say, with their company’s goals. That’s rather creative, but preventing a breach of contract seems like a heavy lift in the current slash-and-burn climate.
In a post criticizing biopharma’s silence in the face of attacks on US science and academia, Derek Lowe argued that industry kowtowing to the regime is likely out of an expectation of some level of government corruption. That could include, he said, the worst case scenario for them, “where government short-circuits into becoming a protection racket.”
Since then, Eli Lilly announced that they will be building 4 new manufacturing plants in the US, apparently in response to a meeting with the President where he threatened 25% tariffs on imported pharmaceuticals. Eli Lilly is one of the manufacturers of weight-loss drugs. The reports haven’t included how much of that development was already planned.
It’s too soon to see how this will all pan out for the prospects for Americans for next generation Covid vaccines, especially with the implications of changes at the FDA still unclear. The most likely prospects for mucosal vaccines in the near future are being developed in Europe, and some of those developers may have a global strategy. The mucosal vaccines that appear to be more advanced in the US seem to be dependent on Project NextGen contracts.
For other types of next generation vaccines, there are several in the US that are not reliant on Project NextGen. There’s no word yet on Arcturus’ plans for seeking FDA approval for Kostaive, the self-amplifying mRNA vaccine. Although that is an American company, manufacturing in the US, an anti-mRNA climate in the US might disrupt that strategy.
CalTech has partnered with a UK company for clinical testing of its pancoronavirus vaccine, but that’s very early days. Gylden Pharma (formerly Emergex) is also a UK/USA partnership for a pancoronavirus vaccine, and it’s a little further along.
Mucosal vaccine news
And then there were 33… This month, another mucosal vaccine has entered human trial – and it aims to prevent infection and be “variant-proof.” There’s funding in Japan for developing inhaled mRNA vaccine. As well, there were 6 preclinical reports of mucosal vaccines this month, including an intranasal mRNA vaccine developed in Singapore.
Intranasal protein subunit vaccine from LovalTech (France) goes into phase 1/2 trial
This nasal spray vaccine, called LVT001, is based on a fusion of SARS-CoV-2 proteins (including spike and nucleocapsid proteins). LovalTech is based in Tours, and the vaccine was developed with public funding, a university, and the national health agency, ANRS (INSERM). LovalTech reports that they have a licensing deal for this vaccine with “a big pharmaceutical company,” but they don’t say which one. They say they hope to launch the vaccine in 2025 – if they mean reach authorization and rollout, that is very ambitious.
There hasn’t been a publication of preclinical results for this vaccine, but there is a summary of preclinical results in mice and hamsters in this slide deck. Although there is little data in the slides, the developers report that challenge studies protected animals against morbidity and mortality from multiple Covid strains, including Delta and Omicron. In addition, there was no transmission of the virus to co-housed animals. (The group published a study on Covid mucosal immunity in human nasal fluid and serum samples in 2023.)
A phase 1/2 clinical trial of this vaccine is planned to start in March. A booster dose of LVT001 will be compared to a booster dose of the BNT/Pfizer Covid vaccine. In phase 1, low, medium, and high doses will be compared for safety and immunogenicity. A total of 238 participants will be involved in the phase 1/2 trial, recruiting in 5 cities, including Paris and Tours. They will be measuring infection rates, as well as signs of nasal immunity.
The trial register entry is here. If you are interested in participating, contact details are here.
Early developmental work on inhaled mRNA vaccine funded in Japan
HiLung is a company based in Kyoto. They have received government funding to develop an inhaled mRNA vaccine for respiratory disease, and test it in rodents. Which respiratory disease is not specified. Their goal is the “development of
powerful mRNA vaccines based on enhanced local immunity and lower toxicity.”
This company’s work is aimed at developing a carrier that can get mRNA vaccine directly into the epithelial cells lining the respiratory tract. The company has been developing a method for producing respiratory epithelial cells called HiREC-Ex. They expect HiREC-Ex to enable scalable production of exosomes which could carry mRNA and deliver it into the body’s respiratory epithelial cells. There is a list of their publications on this work here.
Preclinical reports for mucosal vaccines
I added 6 preclinical studies this month:
- Intranasal mRNA vaccine developed by the Agency for Science, Technology and Research (Singapore): In this report, the developers of an intranasal mRNA vaccine describe tests in mice. They compared it with a vaccine similar to the BNT/Pfizer vaccine, and concluded that it produced much higher mucosal immunity.
- Another study of protection against transmission with the Castlevax intranasal viral vector vaccine (USA): This is one of the vaccines with funding from Project NextGen for a phase 2b “mini-efficacy” trial. It is developed by the Icahn School of Medicine at Mt Sinai. In this new report the developers tested a trivalent version of the vaccine in mice (original virus, Beta, and Delta). The studies included challenge and transmission tests. The authors concluded that a booster after primary mRNA vaccination boosted both systemic and mucosal immunity.
- Intranasal DNA and peptide vaccines developed at Johns Hopkins University (USA): This report describes studies of a DNA vaccine in mice, in injected and intranasal versions. The developers also tested a peptide vaccine version with an adjuvant. They plan to continue testing of the vaccines, alone and in combination.
- An oral viral vector vaccine developed at NTFID, Center for Disease Control & Prevention (China): This oral vaccine is based on Adenovirus 5 and Omicron. The developers report on tests in mice, including comparing it to an mRNA vaccine. As a booster after mRNA vaccine, they report that it boosted both systemic and mucosal immune response.
- An intranasal live attenuated vaccine from Osaka University (Japan): This report describes tests in mice and hamsters of a live attenuated vaccine. Signs of immune response persisted for a year. The developers also report on several tests of safety.
- An intranasal protein subunit vaccine developed by the Statens Serum Institute (Denmark): This report describes tests of an intranasal protein subunit vaccine in mice and hamsters, including challenge tests. The vaccine was compared with the Moderna mRNA vaccine. The developers concluded that the intranasal vaccine produced signs of both systemic and mucosal immunity, while injected versions of the same vaccine or the mRNA one produced predominantly systemic immunity.
Skip ahead to next news category
Mucosal Covid vaccine overview
- 5 mucosal vaccines are currently authorized for use, at least 1 in each of 6 countries. However, none have been authorized by a drug regulatory agency designated stringent, or listed, by WHO.
- 33 mucosal vaccines have reached clinical trial, although some of the vaccines are no longer in development. The vaccines that have entered clinical trials are tracked in a table below.
- In addition to the 5 authorized mucosal vaccines, 4 have reached phase 2 trials, and another 2 have reached phase 2/3 trial.
US Project NextGen-funded trials in this category:
- Phase 1 for MPV/S-2P, the intranasal viral vector vaccine developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). This trial for 60 participants began recruiting in July 2024.
- Phase 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax (planned to start in the last quarter of 2024);
- Phase 2b for the intranasal live attenuated vaccine from Codagenix;
- Phase 2b for the oral viral vector vaccine from Vaxart (trial start announced at the end of September 2024; trial registration here); and
- Phase 2b for the intranasal viral vector vaccine from Blue Lake Biotech/CyanVac (trial started in December 2024, trial registration here).
Durable or “variant-proof” vaccine news
There were 3 major developments in this category this month. One was already reported above: The intranasal vaccine from LovalTech going into clinical trial in France. Another vaccine in this category has gone into clinical trial in the US, too. The biggest news, though, is the authorization in Europe of a self-amplifying mRNA vaccine and the release of the large European independent assessment report.
First next generation Covid vaccine authorized in Europe: Kostaive (zapomeran) self-amplifying mRNA vaccine from Arcturus
The European authorization of Kostaive for adults was announced on Valentine’s Day. That brings the number of Covid vaccines authorized for adults in Europe to 5. The others are 2 mRNA vaccines (from BNT/Pfizer and Moderna), and 2 protein subunit vaccines (from Novavax in the US, and Hipra in Spain).
The full European assessment report (EPAR) for Kostaive was published online on February 26, in English and other European languages, as well as the shorter summary in the product information – with the package leaflet for users at the end (in English and other languages). The EPAR covers 2 versions of the vaccine: ARCT-021 and ARCT-154. Each is authorized for both primary vaccination and annual boosters. Kostaive is the trade name in Europe and Japan, and zapomeran is the international non-proprietary name.
The vaccine is manufactured in the US (with compliance to manufacturing standards certified by a European agency). The EPAR describes a number of quality control steps the European Medicines Agency (EMA) required, including assessments for impurities. The vaccine comes in a lyophilised powder, to be prepared in liquid for injection.
As usual, there is more detail about the vaccine in the EPAR than in the publications for the vaccine.
Conclusions on clinical effects
The independent European assessment confirms the conclusions of the publications: This vaccine has a more durable immune response than the BNT/Pfizer vaccine: There is some waning, but it is “less pronounced.” It is still expected to be boosted annually, with updated versions for new Covid variants.
However, the assessors point out that there is too little data comparing Kostaive with protein subunit vaccines as boosters when people’s primary vaccination was with mRNA. What little data there is, does not suggest the immune response is superior to that you can expect from a protein subunit vaccine.
The assessors were keen to see T-cell data for Kostaive, as theoretically, this type of vaccine could have a stronger effect on this form of immune response. The developers responded that they would extend analysis of T-cell data in ongoing studies.
For the clinical studies, phase 3 data for up to 6 months post-vaccination were included. There is a detailed summary and statistical analysis across all the clinical trials. And from page 150 to 152, there are useful summary tables on effects.
The EMA’s summary of the vaccine reactions are similar to reactions to other mRNA vaccines:
“The most frequent adverse reactions (≥ 10%) after dose 1 or dose 2 are pain at the injection site (49.1%), tenderness at the injection site (49.0%), fatigue (42.3%), headache (35.4%), myalgia (30.1%), chills (28.5%), arthralgia (27.2%), dizziness (20.1%), and pyrexia (10.8%).”
The manufacturer is required to run a surveillance study after rollout, to see if this vaccine has the same rare cardiac adverse effects as other mRNA vaccines, as well as a pregnancy outcomes study. A study in people with compromise immune systems is planned.
The development plan for studying the vaccine in children and adolescents is still in preparation.
More preclinical data
The additional information includes a reproductive toxicity study in rabbits (for ARCT-021), detailed assessment of the vaccine’s new lipid component, immunobridging data for ARCT-154, and data from other early studies of the Arcturus vaccine platform.
The report addresses the burning question that hadn’t been included in the publications: How long the mRNA lasts. In preclinical studies, the EPAR reports that as expected, although it has a lower dose of mRNA, the self-amplifying mRNA results in more RNA exposure after injection than there is from mRNA in current vaccines. That is presumably why the vaccine has a stronger and more durable effect.
However, in animal studies so far, the mRNA clears within weeks, “despite the self-amplifying nature of the construct. Hence, there should be no concern for long term exposure to the active drug substance in the vaccine.” From the product information: “The mRNA self-amplification process is transient and does not generate infectious particles.”
Viral vector vaccine called CoTend from University of California LA (UCLA) and Tendel Therapies going into clinical trial in the US
There’s not a lot of public detail on this one. A phase 1 trial for 80 people has been registered, with a planned start in March. Two versions of the vaccine – with and without an adjuvant – will be tested as a booster, in 5 different doses, with a placebo control.
The developers had an NIH grant to help get the vaccine ready for clinical trial, and there is a little more information with that grant’s details. The vaccine targets T-cells, to aim for a more durable response, and it’s based on Omicron. The developers report that the vaccine without an adjuvant waned in non-human primates by 6 months.
As Tendel Therapies is also California-based, presumably it will be recruiting there. If you’re interested in participating, contact details are here.
Skip ahead to next news category
Durable or “variant-proof” vaccine overview
Note: This is a rather vague category, including vaccines that aim to be more durable. I’m not sure how many can be classified as aiming to be “variant-proof”.
Authorized vaccine:
There is one vaccine in this category that has been authorized by a drug regulatory authority designated by WHO has stringent, or listed – and tested against an mRNA vaccine:
- LUNAR-COV19 (USA), trade name Kostaive: This self-amplifying mRNA vaccine was authorized in Japan in November 2023, with rollout in October 2024. It was also authorized for Europe in February 2025.
US Project NextGen-funded trials in this category:
- Phase 1 for TNX-1800 from Tonix (aiming for lifelong immunity) (planned to go into clinical trial in 2024);
- Phase 2b (“mini-efficacy”) for GeoVax (viral vector vaccine) (planned to go into clinical trial in the second half of 2025).
These trials have not been registered at ClinicalTrials.gov as yet.
Note: Gritstone Bio was originally in line for a phase 2b trial for their self-amplifying mRNA vaccine. However, the company declared bankruptcy and in January 2025, their assets were sold.
Pancoronavirus vaccine news
No news to report in this category.
Pancoronavirus vaccine overview
A table below this post keeps track of vaccines I’ve added to this category so far that have publicly available preclinical results. Of these vaccines, 6 have reached phase 1 clinical trials, with some results for 3 of them marked *:
- * CoronaTcP (Gylden Pharma, UK/US) – protein subunit. (Note: This vaccine was previously called PepGNP-SARSCov2, and the manufacturer was previously called Emergex.)
- DIOSynVax (Cambridge University spin-off, UK) – mRNA.
- INSERM/Ennodc (formerly LinkInVax) (France) – protein subunit.
- Osivax (France) – protein subunit (phase 1 trial fully recruited in June 2024).
- * VBI Vaccines (Canada) – eVLP. [This company announced bankruptcy in late 2024.]
- * Walter Reed Army Institute of Research (WRAIR, USA) – protein subunit.
US Project NextGen-funded trials in this category:
- CoronaTcP (Gylden Pharma, UK/US) – protein subunit.
- Unnamed (PopVax, India) – mRNA.
Addendum 1: List of authorized next generation Covid vaccines (with countries)
There are now 7 next-generation Covid vaccines authorized in 7 countries. Only one has been authorized or approved by drug regulatory agencies designated stringent, or listed, by WHO – in bold. Authorization is pending in the European Union. I’ve listed the vaccines in 2 categories, in order of date of first authorization (or initial approval).
Mucosal:
- Razi-Cov Pars (Iran), intranasal protein subunit vaccine: Iran (October 2021).
- Sputnik (Russia), intranasal viral vector vaccine: Russia (April 2022).
- Convidecia (China), inhaled viral vector vaccine: China (September 2022), Morocco (November 2022), Indonesia (March 2023).
- iNCOVACC (USA/India), intranasal viral vector vaccine: India (September 2022).
- Pneucolin (China), intranasal viral vector vaccine: China (December 2022).
Self-amplifying mRNA:
- Gemcovac (India): India (June 2022).
- Kostaive (LUNAR-COV19) (USA): Japan (November 2023), initial European approval, authorization pending (December 2024).
Addendum 2: Table of mucosal vaccines in clinical trials
* Indicates new entry since previous update post.
Note: Where there is a link to “All records” for a vaccine, that’s in my public Zotero collection for the vaccine, and it may include non-mucosal studies for that vaccine. Notes on that collection are here. For details on how I track Covid vaccine progress to maintain that collection, see my background post.
| Vaccine, type, manufacturer | Mucosal version(s) | Phase 1 to 2 clinical trials | Phase 3+ trial(s) | Phase 3+ efficacy or immunogenicity results |
|---|---|---|---|---|
| ACM-001 Protein subunit ACM Biolabs (Singapore/Switzerland) (All records) | Intranasal. | Phase 1. Results (press release only) | ||
| Ad5-nCoV (Convidecia Air) Viral vector (adenovirus) CanSino (China) (All records) | Inhaled through the mouth using a nebulizer. | Phase 1. Results. Phase 1/2. Results (plus second later preprint). Phase 1/2. Results. Phase 2 (aged 6-17 years). Booster adapted for variant. | 10,420 people in China (Phase 3). Results. 1,350 people (Phase 3). 540 people, in Malaysia (Phase 3). Results. 904 people in China (Phase 4). Results. 360 people (Phase 4). 451 people (Phase 4). Results. 10,000 people in China (Phase 4). Results for a 4,089 in the Ad5-nCoV arms. | 904 people: Comparison after 2-dose course of inactivated vax: Convidecia injection vs inhaled, protein subunit, or CoronaVac booster (Phase 4 results). Both injected & inhaled Convidecia had stronger impact on signs of immunity than the others; response after inhaled version was slower but longer-lasting than injected (which peaked then declined from day 14), better for Omicron though not as good for original virus. No measure of mucosal immunity used. 539 people (Malaysia): Signs of serum immune response were lower for inhaled Convidecia than for injected BNT/Pfizer vax at 14 days, but grew for Convidecia to similar levels. Mucosal immune response (SIgA) was greater for Convidecia; the rate of adverse reactions was lower. 451 people: Comparison of different versions adapted for variant, including a bivalent version. Booster of inhaled Convidecia after previous vaccination with inactivated vaccine. Signs of immune response to Omicron were higher for the bivalent vaccine, though lower for the original SARS-CoV-2 strain. 4,089 people, plus a 2,008 un-randomized unboosted control group: This trial tested the original vax during Omicron, with either an injected or inhaled booster. There wasn’t a significant difference between them, though the injected version fell below their ineffectiveness threshold and the inhaled one reached effectiveness despite having a smaller dose of vaccine. |
| Ad5-S Viral vector (adenovirus) State Key Laboratory for Infectious Disease/Guangzhou Enbao Biomedical Technology Co (China) (All records) | Intranasal. | Infection prevention study. | ||
| AdCOVID Viral vector (adenovirus) AltImmune (USA) (All records) | Intranasal. | Phase 1. Results – press release only. Discontinued after phase 1. | ||
| AdS+N Viral vector (adenovirus) ImmunityBio (USA) (All records) | Intranasal, oral capsule, or sublingual. | Phase 1 (oral). Phase 1 (sublingual). | ||
| AeroVax (Ad5-triCoV) Viral vector (adenovirus) McMaster University/Canadian Institutes of Health Research (Canada) (All records) | Aerosol. | Phase 1 (& ChAd-triCoV/Mac). Phase 2. Short protocol. | ||
| Avacc 10 Protein subunit Intravacc (Netherlands) (All records) | Intranasal. | Phase 1. Results (press release only) | ||
| bacTRL-Spike-1 Live attenuated Symvivo (Canada) (All records) | Oral. | Phase 1. | ||
| BBV154 (iNCOVACC) Viral vector (adenovirus) Bharat Biotech (India) (All records) This vaccine is ChAd-SARS-CoV-2-S Washington University in St Louis (USA) (All records) | Intranasal. | Phase 1. Phase 2. Small amount of data from these trials in the drug product information. Phase 2/3. Phase 2. | In India, 2-dose course of BBV154 vs 2-dose course of injected Covaxin inactivated vaccine (Phase 3 – and here). Results (previously in preprint). See also the drug product information. 875 people in India, booster trial (Phase 3). | 2,971 previously unvaxed people were assigned for the intranasal iNCOVACC, 161 for injected Covaxin. This trial did not aim to assess disease outcomes. It took place during the first Omicron wave. Signs of immune response were higher for iNCOVACC than Covaxin. Adverse events rate very low (5% local and 3% systemic) – lower than for comparison group. |
| B/HPIV3/S-6P Viral vector (parainfluenza) NIH’s National Institute of Allergy and Infectious Diseases (NIAID) (USA) (All records) | Intranasal. | Phase 1. Fully recruited by early July 2024. | ||
| BV-AdCoV-1 Viral vector (adenovirus) Wuhan BravoVax (China) (All records) | Inhaled through the mouth using a nebulizer. | Phase 1. | ||
| ChAdOx1 Viral vector (adenovirus) Oxford University (UK) (This is the AstraZeneca vax) (All records) | Intranasal. | Phase 1. Phase 1. Results. | ||
| CoV2-OGEN1 Protein subunit US Specialty Formulations/VaxForm (USA) (All records) | Oral. | Phase 1. (Fully recruited, final dose in November 2022.) Press release stating successful (without data) and progressing to phase 2 trial. | ||
| COVI-VAC Live attenuated Codagenix (USA, with the Serum Institute of India) (All records) | Intranasal. | Phase 1. Press release in 2021 stating successful (without data) and progressing to phase 2/3. Preliminary results (conference abstract in 2021) and in a 2022 press release. Results in 2023 (press release only). Phase 1 (booster). | Phase 2/3, as part of the WHO Solidarity Trial for Vaccines in Mali, Colombia, Kenya, Philippines, Sierra Leone. Fully recruited by July 2024. (Protocol.) | |
| CVXGA1-001 Viral vector (parainfluenza) CyanVac/Blue Lake Tech (USA) (All records) | Intranasal. | Phase 1. Results (press release only). Phase 2. Results (press release only). Phase 2b. | ||
| DNS1-RBD (Pneucolin) Viral vector (influenza) Beijing Wantai BioPharm (China) (All records) | Intranasal. | Phase 1. Phase 2. Joint results. | 30,990 participants in Colombia, Philippines, South Africa, Vietnam. Results (previously in preprint.) 5,400 participants in Ghana (Phase 3). | Comparison of 2 doses of intranasal vaccine 14 days apart, with placebo control, during circulation of Omicron. Included >13,000 previously unvaccinated people. Efficacy shown 90 days after 2nd dose. There was some decline at 180 days. Efficacy against symptomatic Covid: No previous vax: 55.2% (CI 13.8 to 76.7) Inactivated: 38.2% (CI -49.2 to 74.4) Viral vector: 39.9% (CI -16.7 to 69.1) mRNA: 10.1% (CI -45.9 to 44.5) Efficacy against severe Covid: No previous vax: 66.7% (CI 8.3 to 87.9) Inactivated: 54.6% (CI -47.3 to 86.0) Viral vector: 50.0% (CI -6.8 to 76.6) mRNA: 19.5% (CI -39.2 to 53.4) Efficacy against hospitalization: 100% (CI -9.2 to 100) Adverse events were very low – similar to placebo. Less than 8% of people had a runny and/or blocked nose or sore throat. |
| FINCoVac Viral vector (adenovirus) Rokote Laboratories (Finland) | Intranasal. | Phase 1. | ||
| GAM-COVID-VAC (rAd26-S – Sputnik Light) Viral vector (adenovirus) Gamaleya Research Institute (Russia) | Intranasal. | Phase 1/2. | 7,000 participants in Russia (Phase 3 or phase 2/3 – not clear). | |
| * LVT001 Protein subunit LovalTech (France) | Intranasal. | Phase 1/2. | ||
| Mambisa Protein subunit Centre for Genetic Engineering & Biotechnology (CIGB) (Cuba) (All records) | Intranasal drops. | Phase 1/2. Phase 1/2. Results. Phase 2. | ||
| MPV/S-2P Viral vector (murine pneumonia) National Institute of Allergy and Infectious Diseases (NIAID) (USA) (All records) | Intranasal drops. | Phase 1. | ||
| MV-014-212 Viral vector (RSV) Meissa Vaccines (USA) (All records) | Intranasal drops or spray. | Phase 1. Results (press release). | This vaccine is in limbo because of the company’s financial difficulties. | |
| MVA-SARS-2ST Viral vector (MVA) German Centre for Infection Research (DZIF)/IDT Biologika (All records) | Inhalation. | Phase 1. | ||
| NB2155 Viral vector (Adenovirus 5) Guangzhou Medical University/ Guangzhou National Laboratory (All records) | Intranasal. | Phase 1. | ||
| CVAX-01 Viral vector (Newcastle Disease Virus) Castlevax/Icahn Mt Sinai (All records) | Intranasal. | Phase 1. Results (press release). | ||
| Ad5-S-Omicron BA.1 Viral vector (Adenovirus 5) Guangzhou Medical University/Guangzhou National Laboratory (China) (All records) | Intranasal | Phase 1. Results. | ||
| Patria (NDV-HXP-S/AVX-COVID-12-HEXAPRO) Viral vector (Newcastle Disease Virus) Laboratorio Avi-Mex (Mexico) (All records on Patria, see also CVAX-01 for early development.) | Intranasal. | Phase 1. Results. Phase 2. Results. (Previously available in preprint.) | Phase 2/3 for injected version only: Results. | |
| PRAK-03202 Protein subunit Oravax (USA) [Oravax was established by OraMed (Israel) to develop this vaccine, using Premas Biotech’s PRAK-03202 and their oral vaccine technology] (All records on oral PRAK-03202, and on intramuscular version) | Oral. | Phase 1 (in South Africa). Results (press release only). | ||
| Razi-Cov Pars Protein subunit Razi Vaccine & Serum Research Institute (Iran) (All records) | Intranasal (third dose after 2 injections). | Phase 1. Results. Phase 2. Results. Phase 1 to 2 (in 12-17 year-olds). Phase 4 (Booster). Results. Phase 1 to 2 (in 5-17 year-olds). | 41,128 people in Iran, comparing the 3-dose course to 2-dose inactivated Sinopharm Beijing vax, only partially randomized (Phase 3). Results (Previous media report for the first 24,000 participants.) | Phase 3: The authors concluded Razi-Cov Pars was non-inferior to the inactivated vaccine, with similarly very low adverse events. However, the trial could not establish whether there was an advantage to an intranasal dose. Phase 4: Immunogenicity and safety study of intranasal booster in 195 people, placebo-controlled. Increased IgA and IgG anti-RBD in nasal mucosa, but not in serum and saliva. |
| SC-Ad6-1 Viral vector (adenovirus) Moat Bio/Tetherex (USA) (All records) | Intranasal and inhaled. | Phase 1. Trial expanded to add an inhaled version (from 130 to 190 people). Results so far briefly mentioned in press release. | ||
| SpikoGen Protein subunit Vaxine (Australia) (All records on mucosal and on all forms.) | Oral/sublingual. | Phase 1. | ||
| (Unnamed) Inactivated bacteria DreamTec (Hong Kong) (All records) | Oral. | Phase 1. Phase 1. Phase 1. Note: An article of preclinical results has been retracted over lack of ethics committee approval. | ||
| VXA-CoV2-1/VXA-CoV2-1.1-S Viral vector (adenovirus) Vaxart (USA) (All records) | Tablets. | Phase 1. Results. Phase 2. (Started October 1, 2021.) Results (press release). Additional brief results in presentation. Phase 2b. (Start announced September 30, 2024.) |
Addendum 3: Pancoronavirus vaccines with preclinical results
| Developer Country Vaccine name | Type of: Vaccine Coronavirus | Preclinical results | Clinical trial status |
|---|---|---|---|
| Academia Sinica Taiwan (Taiwan) (Unnamed) | mRNA All | Non-primate | |
| Baylor College of Medicine (USA) (Unnamed) | Protein subunit Beta | Non-primate | |
| Beijing University of Chemical Technology (China) (Unnamed) | Live attenuated pangolin coronavirus All | Non-primate | |
| Beth Israel Deaconess Medical Center USA RhAd52.CoV.Consv | Viral vector Sarbeco | Non-primate | |
| California Institute of Technology (Caltech), Ingenza USA, UK Mosaic-8b | Protein subunit Beta | Non-primate Non-primate Primate, non-primate Non-primate (previously in preprint) Non-primate (previously in preprint) Primate and non-primate | |
| Charité Universitätsmedizin Berlin Germany NILV-PanCoVac | Viral vector All | Non-primate (mucosal) | |
| China Cuba Joint Innovation Center China, Cuba Unnamed | Protein subunit Sarbeco | Non-primate (mucosal) Non-primate (mucosal) | |
| Codiak USA exoVACC Pan Beta Coronavirus | Protein subunit Beta | Article on development Non-primate (conference slides) Non-primate (conference slides) | (This company began proceedings in bankruptcy court. See news.) |
| DIOSynvax UK DIOS-CoVax/ pEVAC-PS | mRNA Sarbeco | Non-primate Non-primate Non-primate (a different vaccine) | Phase 1 trial (incl. protocol) (Up to 36 participants in the UK) Began December 2021. Fully recruited. Expanded to another city – no trial register entry found. |
| Duke University USA RBD–scNP | Protein subunit Beta | Primate Primate Primate, non-primate Non-primate (previously in preprint) Primate, non-primate | |
| Francis Crick Institute UK (Unnamed) | Protein subunit with DNA boost All | Non-primate | |
| Fudan University China HR1LS | Protein subunit Sarbeco | Primate, non-primate Primate Primate Non-primate | |
| Georgia State University, University of Iowa USA SARS2-S (SARS-RBD) | mRNA Sarbeco | Non-primate Non-primate | |
| Georgia State University USA Om-S-MERS-RBD | Protein subunit All | Non-primate | |
| Georgia State University USA (Unnamed) | Protein subunit Sarbeco | Non-primate Primate, non-primate Non-primate | |
| Guangdong Pharmaceutical University China (Unnamed) | Protein subunit All | Non-primate | |
| Gylden Pharma (formerly Emergex) UK/USA CoronaTcP | Protein subunit Beta | Phase 1 trial (26 participants in Switzerland) Results. (Formerly press release only) Phase 1/2 trial (Up to 110 participants in the Philippines) (Not yet recruiting) | |
| Korea Research Institute of Bioscience and Biotechnology South Korea (Unnamed) | Protein subunit Sarbeco | Non-primate | |
| INSERM Vaccine Research Institute/Ennodc (formerly LinKinVax) France PanCov (CD40.CoV2/RBDv) | Protein subunit Sarbeco | Non-primate Primate, non-primate Primate Non-primate (conference poster) Non-primate | Phase 1/2 trial (Up to 240 participants in France) Booster trial; began recruiting in May 2024. |
| Osivax France OVX033 | Protein subunit Sarbeco | Non-primate | Phase 1 trial (48 participants in France) First participant vaccinated in February 2024. Fully recruited in June 2024. |
| Oxford University UK ChAdOx1.COVconsv12 | Viral vector Sarbeco | Non-primate | |
| Pennsylvania State University USA (Unnamed) | Protein subunit All | Non-primate | |
| Scripps Research Institute USA (Unnamed) | Protein subunit Beta | Non-primate | |
| Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University China rTTV-RBD-HA2 | Viral vector Beta (plus influenza) | Non-primate (mucosal) | |
| SK Bioscience/ Uni of Washington/Uni of North Carolina at Chapel Hill South Korea, USA GBP511 | Protein subunit Sarbeco | Primate, non-primate (testing Covid vaccine GBP510 against other sarbecoviruses) | More on plans for adapting this vaccine – GBP510 authorized as SKYCovione. See the University of Washington research listed below in this table. |
| Stanford University USA DCFHP-alum | Protein subunit Sarbeco | Primate Erratum (correction to legend in a figure). Non-primate | |
| Stanford University USA Unnamed | Protein subunit All | Non-primate | |
| State Key Laboratory of Respiratory Disease Guangzhou Medical University China (Unnamed) | Protein subunit Sarbeco | Primate and non-primate | |
| Sun Yat-Sen University China (Unnamed) | Protein subunit Sarbeco | Non-primate | |
| University of Amsterdam Netherlands (Unnamed) | Virus-like particle Sarbeco | Non-primate | |
| University of California Irvine/Techimmune USA (Unnamed) | Viral vector Beta | Non-primate (previously in preprint) Non-primate (mucosal) (previously in preprint) Non-primate (There was also a paper about this vaccine’s development in 2021.) | |
| University of Houston/Auravax USA NanoSTING-NS | Protein subunit (intranasal) Sarbeco | Non-primate Non-primate Non-primate Primate, non-primate | |
| University of North Carolina at Chapel Hill USA (Unnamed) | Viral vector Sarbeco | Non-primate (Previously in preprint) | |
| University of North Carolina at Chapel Hill USA (Unnamed) | mRNA Sarbeco | Non-primate | |
| University of Sydney Australia CoVEXS5 | Protein subunit Sarbeco | Non-primate | |
| University of Toronto Canada (Unnamed) | Protein subunit Sarbeco | Non-primate | |
| University of Washington USA (Unnamed) | Protein subunit Sarbeco | Non-primate (Previously in preprint) Non-primate Non-primate (MERS vaccine developed on the same platform as GBP511.) | (See “GBP511” above in this table.) |
| University of Wisconsin-Madison (PanCorVac) USA (Unnamed) | Protein subunit All | Non-primate Non-primate Non-primate Non-primate (previously in preprint) | |
| VBI Vaccines Canada VBI-2901 | eVLP All | Non-primate Non-primate (Press release) | This company declared bankruptcy in late 2024. Phase 1 trial (103 participants in Canada) Began October 2022. Fully recruited. (Further background info.) Results (press release only). (101 participants) Previously vaccinated people boosted with 2 low or high doses, or 1 high-dose. Limited data reported. Some signs of immune response to a range of coronaviruses, mostly lasting at least 5 months. No major safety concerns. |
| Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan Canada Unnamed | Protein subunit Sarbeco | Non-primate | |
| Walter Reed Army Institute of Research (WRAIR) USA SpFN/ALFQ | Protein subunit Beta | Non-primate Non-primate Non-primate (incl RFN) Non-primate Primate Primate Primate (with J&J vax) | Phase 1 trial (US) Began April 2021, with 29 participants, including some on placebo. Results. Vaxed participants showed immune responses to several Covid variants and several sarbecoviruses, but no signs of response to MERS. |
| Walter Reed Army Institute of Research (WRAIR) USA RFN | Protein subunit Beta | Non-primate (incl SpFN) Primate | |
| Washington University in St Louis USA (Unnamed) | Viral vector Sarbeco | Non-primate (mucosal) | |
| Yale University USA (Unnamed) | mRNA All | Non-primate Non-primate | |
| Yale University/Xanadu Bio USA (Unnamed) | Protein subunit, intranasal booster Sarbeco | Non-primate |
Addendum 4: Definitions of vaccine types
- Mucosal vaccines: These enter the body the way the virus does – through mucosal tissues. It’s hoped that provides defence against infection. They can be administered via different routes – squirts or drops in the nose, inhaled through the mouth through a nebulizer (similar to an asthma medication), or in tablet, capsule, or sublingual form.
- Pan-SARS-CoV-2 or “variant-proof” vaccines: These aim to provide protection against any variant of the coronavirus that causes Covid-19 – including future variants. I include vaccines that aim for greater durability in this group. Pancoronavirus vaccines can be targeted to:
– the “subgroup” the 2 SARS viruses came from (the sarbecovirus subgenus),
– coronaviruses from the next level up (the genus, betacoronavirus, which includes lethal diseases like MERS, as well as common cold viruses), or
– the whole coronavirus family, with 4 genuses, including betacoronavirus and alphacoronavirus (with more common cold viruses).
I classify a vaccine as a pancoronavirus one when the developers are explicitly targeting coronaviruses more broadly than SARS-CoV-2, and have tested for signs of response to non-SARS-CoV-2 coronavirus(es) (or clearly plan to).
You can keep up with my work at my newsletter, Living With Evidence. And I’m active on Mastodon: @hildabast@mastodon.online and less so on BlueSky (hildabast.bsky.social).
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For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.
Previous update posts specifically on next generation Covid vaccines prior to this monthly series (beginning May 2023):
- Mucosal vaccines (March 2022)
- Pan-SARS-Cov-2 and pancoronavirus (July 2022)
- Mucosal vaccines (July 2022)
- Mucosal vaccines (September 2022)
- Mucosal vaccines (April 2023)
- Pancoronavirus vaccines (April 2023)
All my posts on Covid vaccines, beginning from March 2020, are tagged here.
All previous Covid-19 posts at Absolutely Maybe
My posts at The Atlantic and at WIRED.
Disclosures: My interest in Covid-19 vaccine trials began as a person worried about the virus, as my son was immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not one working on vaccines. More about me.
The cartoon is my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)